Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10321)
Regulator Name Growth/differentiation factor 15 (GDF15)
Synonyms
Macrophage inhibitory cytokine 1; NSAID-activated gene 1 protein; NSAID-regulated gene 1 protein; Placental TGF-beta; Placental bone morphogenetic protein; Prostate differentiation factor
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Gene Name GDF15
Gene ID 9518
Regulator Type Protein coding
Uniprot ID Q99988
Sequence
MPGQELRTVNGSQMLLVLLVLSWLPHGGALSLAEASRASFPGPSELHSEDSRFRELRKRY
EDLLTRLRANQSWEDSNTDLVPAPAVRILTPEVRLGSGGHLHLRISRAALPEGLPEASRL
HRALFRLSPTASRSWDVTRPLRRQLSLARPQAPALHLRLSPPPSQSDQLLAESSSARPQL
ELHLRPQAARGRRRARARNGDHCPLGPGRCCRLHTVRASLEDLGWADWVLSPREVQVTMC
IGACPSQFRAANMHAQIKTSLHRLKPDTVPAPCCVPASYNPMVLIQKTDTGVSLQTYDDL
LAKDCHCI

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Family TGF-beta family
Function
Regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses. Binds to its receptor, GFRAL, and activates GFRAL- expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem. It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitutes part of the 'emergency circuit' that shapes feeding responses to stressful conditions. On hepatocytes, inhibits growth hormone signaling.

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HGNC ID
HGNC:30142
KEGG ID hsa:9518
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
GDF15 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Spinal cord injury ICD-11: ND51
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 rPNs (Rat primary neurons)
In Vivo Model
Total of 50 C57BL/6J adult mice (males, average weight of 20 g, 8 weeks of age) were acquired from Charles River (Beijing, China). In brief, ketamine (80 mg/kg) was utilized to anesthetize mice before the skin was prepared for disinfection, and then the back skin was incised to expose the lamina at T10. Finally, a moderate contusion (5 g x 5 cm) was created by an impactor (RWD, Shenzhen, China). Spinal cord hemorrhage, hindlimb extension, and delayed paralysis suggest successful modeling. Only laminectomy was performed in the Sham group.

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Response regulation GDF15 effectively alleviated neuronal ferroptosis post spinal cord injury (SCI) via the p62-Keap1-Nrf2 signaling pathway and promoted locomotor recovery of SCI mice, which is suggested as a potential target on SCI pathogenesis and treatment.
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MGC-803 cells Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
Response regulation GDF15 knockdown promotes erastin-induced ferroptosis in gastric cancer cell MGC803 by attenuating the expression of SLC7A11 and the function of system Xc-.
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Growth/differentiation factor 15 (GDF15) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MGC-803 cells Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
Response regulation GDF15 knockdown promotes erastin-induced ferroptosis in gastric cancer cell MGC803 by attenuating the expression of SLC7A11 and the function of system Xc-.
Spinal cord injury [ICD-11: ND51]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Growth/differentiation factor 15 (GDF15) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 rPNs (Rat primary neurons)
In Vivo Model
Total of 50 C57BL/6J adult mice (males, average weight of 20 g, 8 weeks of age) were acquired from Charles River (Beijing, China). In brief, ketamine (80 mg/kg) was utilized to anesthetize mice before the skin was prepared for disinfection, and then the back skin was incised to expose the lamina at T10. Finally, a moderate contusion (5 g x 5 cm) was created by an impactor (RWD, Shenzhen, China). Spinal cord hemorrhage, hindlimb extension, and delayed paralysis suggest successful modeling. Only laminectomy was performed in the Sham group.

    Click to Show/Hide
Response regulation GDF15 effectively alleviated neuronal ferroptosis post spinal cord injury (SCI) via the p62-Keap1-Nrf2 signaling pathway and promoted locomotor recovery of SCI mice, which is suggested as a potential target on SCI pathogenesis and treatment.
References
Ref 1 Growth Differentiation Factor 15 Regulates Oxidative Stress-Dependent Ferroptosis Post Spinal Cord Injury by Stabilizing the p62-Keap1-Nrf2 Signaling Pathway. Front Aging Neurosci. 2022 Jul 4;14:905115. doi: 10.3389/fnagi.2022.905115. eCollection 2022.
Ref 2 GDF15 knockdown promotes erastin-induced ferroptosis by decreasing SLC7A11 expression. Biochem Biophys Res Commun. 2020 May 28;526(2):293-299. doi: 10.1016/j.bbrc.2020.03.079. Epub 2020 Mar 21.